Sensory receptors are composed of specialized cells or nerve endings which transduce specific stimuli into neurally encoded messages. The sensory receptors that are the focus of this Program Project Grant (i.e., zebrafish olfactory receptors, arterial chemoreceptors of the carotid body, and Merkel cell mechanoreceptors of the skin) include both "simple" receptors, where the primary afferent neuron is excited directly by the sesory stimulus, and "composite" receptors, in which specialized pre-neural cells are important for stimulus transduction. Cellular machinery mediating sensory transduction includes second messenger pathways and other cellular elements commonly utilized by cells to process diverse biological signals. The collective objective of the proposed research is the analysis of essential elements in signal transduction pathways common to a variety of sensory receptors, as well as an elucidation of those regulatory features unique to specific receptor systems. In this endeavor, a multidisciplinary and collaborative research program will facilitate the exchange of ideas and data, and will support the mutual progress of the constituent projects. The first project will use biophysical and fluorencence ratio imaging techniques to study the mechanistic basic of sex-based differences in the sensitivity of the olfactory organ of zebrafish. The second project will investigate signaling pathways in the arterial chemoreceptors of the mammalian carotid body using biophysical, neurochemical and immunocytochemical methods to explore second messenger cascades, and the role of protein phosphorylation in the transduction and modulation of chemosensory stimuli. Finally, using similar experimental approaches and an in vitro skin/nerve preparation. The third project will examine the mechanisms by which preneural Merkel cells modulate afferent impulse generation in type I sensory neurons.